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GF120918 has a high inhibitory effect on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). We developed [(11)C]GF120918 as a positron emission tomography (PET) probe to assess if dual modulation of P-gp and BCRP is useful to evaluate brain penetration. PET studies using [(11)C]GF120918 were conducted on P-gp and/or Bcrp knockout mice as well as wild-type mice. In PET studies, the AUC(brain) ([0-60 min]) and K (1) value in P-gp/Bcrp knockout mice were nine- and 26-fold higher than that in wild-type mice, respectively. These results suggest that brain penetration of [(11)C]GF120918 is related to modulation of P-gp and BCRP and is limited by two transporters working together. PET using [(11)C]GF120918 may be useful for evaluating the function of P-gp and BCRP. PET using P-gp/Bcrp knockout mice may be an effective method to understand the overall contributions the functions of P-gp and BCRP.


Kazunori Kawamura, Tomoteru Yamasaki, Fujiko Konno, Joji Yui, Akiko Hatori, Kazuhiko Yanamoto, Hidekatsu Wakizaka, Makoto Takei, Yuichi Kimura, Toshimitsu Fukumura, Ming-Rong Zhang. Evaluation of limiting brain penetration related to P-glycoprotein and breast cancer resistance protein using [(11)C]GF120918 by PET in mice. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 2011 Feb;13(1):152-60

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PMID: 20379788

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